2-(2,2-Dimethoxyethyl)-1,3-dithiane → HCID 22335039, compound

HRID 586375Notes

Reaction equation

HRID 586375 reaction equation
[Li]CCCC.[CH3:6][O:7][CH:8]([O:16][CH3:17])[CH2:9][CH:10]1[S:15][CH2:14][CH2:13][CH2:12][S:11]1.[Cl:18][C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([CH3:30])=[C:26]([CH2:28]Cl)[N:27]=2)[CH:24]=1>C1COCC1>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([CH3:30])=[C:26]([CH2:28][C:10]3([CH2:9][CH:8]([O:7][CH3:6])[O:16][CH3:17])[S:15][CH2:14][CH2:13][CH2:12][S:11]3)[N:27]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 131670152-(2,2-Dimethoxyethyl)-1,3-dithianeHCID 22335102HCID 22335102, compoundHCID 178418339Butyllithium

Product 1

HCID 22335039HCID 22335039, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

A solution of n-BuLi in hexanes (1.6 M, 1.4 mL) is added dropwise at −50° C. to a solution of 2-(2,2-dimethoxy-ethyl)-[1,3]dithiane (450 mg, prepared according J. Het. Chem, 1987, 1221) in THF. The mixture is then warmed to −30° C. for 1 hour. After cooling to −50° C., a solution of 6-chloro-2-chloromethyl-3-methyl-imidazo[1,2-a]pyridine (300 mg) in 3 mL of THF is added dropwise; the reaction mixture is then slowly warmed to room temperature. After quenching with aqueous NH4Cl solution, the mixture is extracted with ethyl acetate. The extract is washed with brine, dried over Na2SO4 and concentrated under vacuum. The residue is purified on flash chromatographic column, eluting with 5% MeOH in CH2Cl2, to give 6-Chloro-2-[2-(2,2-dimethoxy-ethyl)-[1,3]dithian-2-ylmethyl]-3-methyl-imidazo[1,2-a]pyridine. 1H NMR (CDCl3, ppm): 7.80 (s, 1H); 7.50(d, 1H); 7.05(d, 1H); 4.80(t, 1H); 3.40(m, 8H); 2.75-3.00(m, 4H); 2.40-2.50(m, 5H); 1.80-2.05(m, 2H). Step 2. Preparation of 6-Chloro-2-[2-(6-fluoro-pyridin-2-yl)-2H-pyrazol-3-ylmethyl]-3-methyl-imidazol[1,2-a]pyridine

Workup

  1. temperatureAfter cooling to −50° C.
  2. temperaturethe reaction mixture is then slowly warmed to room temperature
  3. customAfter quenching with aqueous NH4Cl solution
  4. extractionthe mixture is extracted with ethyl acetate
  5. washThe extract is washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customThe residue is purified on flash chromatographic column
  9. washeluting with 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-cdb036a972144dc3ba74c100652fa566
Source dataset
uspto-grants-2005_08
Patent number
US06936617B2

Reaction notes

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